pci-32765 and Ventricular-Fibrillation

Ibrutinib is an oral inhibitor of Bruton tyrosine kinase approved for the treatment of chronic lymphocytic leukaemia, mantle cell lymphoma and refractory Waldenstrom's disease. It increases progression-free survival, overall survival, response rate. The most frequent adverse reactions, are increased risk in of bleeding and atrial fibrillation, but several reports of more dangerous rhythm disturbances have been recently reported in literature. A case of a patient with refractory Waldenstrom's disease, who developed ventricular fibrillation while taking ibrutinib, is reported, along with a concise literature review.

Topics: Adenine; Death, Sudden, Cardiac; Electrocardiography; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Ventricular Fibrillation; Waldenstrom Macroglobulinemia

Atrial fibrillation is a side effect of ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase used for treatment of B-cell lymphoproliferative disorders. We determined if single (2 or 10 mg/kg), or chronic (14 days) oral ibrutinib followed by 24-hour washout conferred susceptibility to electrically induced arrhythmias in 1-month-old male C57BL/6 mice. A single higher dose of ibrutinib increased arrhythmia inducibility. There was no inducibility difference after chronic dosing with washout. This suggests that high serum drug levels might be responsible for the proarrhythmic effect of ibrutinib and that an altered dosing strategy might mitigate the side effects.

Topics: Adenine; Animals; Atrial Fibrillation; Disease Models, Animal; Disease Susceptibility; Dose-Response Relationship, Drug; Electrocardiography; Male; Mice; Mice, Inbred C57BL; Piperidines; Pulse Therapy, Drug; Pyrazoles; Pyrimidines; Random Allocation; Reference Values; Risk Assessment; Ventricular Fibrillation

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Cohort Studies; Female; Follow-Up Studies; Humans; Lymphoma; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Ventricular Fibrillation